Project Summary My long-term career goal is to become an independent investigator conducting research in the neurobiological basis for language processing in a research university. I propose to attain this goal through a study of language comprehension in a real-world context that extends beyond decoding the traditional phonetic, semantic, and syntactic components of speech. To fully appreciate speaker meaning, listeners must often engage in additional inferential processes. In natural conversation, this includes the use of indirect speech acts to communicate. Consider, for example, if John asks Mark, ?Do you want some cake for dessert?? and Mark replies, ?I am on a diet.? In this exchange, John can infer that Mark does not want dessert, even though it is not explicitly stated. The proposed project will use advanced neuroimaging techniques to examine the neural networks that support processing indirect speech acts such as this one. Hypothesis: Historically, the core language network is thought to consist of two main processing hubs located in left hemisphere peri-Sylvian cortex: the inferior frontal gyrus and the posterior superior temporal gyrus. However, these initial studies were based primarily on assessments of single word and sentence processing. I hypothesize that high-level language comprehension in a conversational context engages additional neural networks typically associated with social cognition and executive function. Aim 1: Characterize the patterns of neural activity and functional connectivity supporting indirect speech act processing in young adults using functional magnetic resonance imaging. Aim 2: Obtain converging evidence for the neuroanatomic basis of indirect speech act comprehension by studying patients with focal neurodegenerative disease due to frontotemporal dementia using structural magnetic resonance imaging. The experiments proposed here will provide the necessary knowledge to lead an independent laboratory investigating the neurobiology of language. The proposed work will aid in characterizing the functional architecture of the language system with converging evidence from healthy and populations with a focal dementia. Improved understanding of brain circuitry supporting high-level language comprehension has important implications for theories of language processing and future treatment studies using neuromodulatory techniques like TMS or tDCS to improve language performance in communicatively impaired populations. Validated assessment of elements of functional communication such as indirect speech acts has important implications for safety and quality of life in patient populations.! !